An six-amino acid motif in the alpha3 domain of MICA is the cancer therapeutic target to inhibit shedding.
An six-amino acid motif in the alpha3 domain of MICA is the cancer therapeutic target to inhibit shedding.
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DOI：
10.1016/j.bbrc.2009.07.062
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发表时间：
2009-09-25
影响因子：
3.1
通讯作者：
Wu, Jennifer D.
中科院分区：
文献类型：
--
作者：
Wang, Xuanjun;Lundgren, Ashley D.;Singh, Pragya;Goodlett, David R.;Plymate, Stephen R.;Wu, Jennifer D.
关键词：
肿瘤细胞表面MHC I类链相关分子A和B（云母/B）的表达可向免疫受体NKG 2D发出信号以进行肿瘤免疫破坏。然而，发现MIC由癌症患者中的肿瘤释放，其负调节宿主免疫并促进肿瘤免疫逃避和进展。肿瘤脱落MIC的机制还不清楚，尽管不同的酶组被认为参与其中。这些酶的功能复杂性使得它们不适合用于抑制MIC脱落的治疗靶标。在这里，我们确定了MIC的α3结构域中的六个氨基酸（6-aa）基序，该基序对于MIC与ERp 5的相互作用至关重要，从而能够脱落。该基序中的突变阻止MIC脱落，但不干扰NKG 2D介导的MIC识别。我们的研究表明，6-aa基序是一个可行的目标，以抑制MIC脱落的癌症治疗。
Expression of the MHC class I chain-related molecules A and B (MICA/B) on tumor cell surface can signal the immune receptor NKG2D for tumor immune destruction. However, MIC was found to be shed by tumors in cancer patients, which negatively regulates host immunity and promotes tumor immune evasion and progression. The mechanisms by which tumors shed MIC are not well understood although diverse groups of enzymes are suggested to be involved. The functional complexity of these enzymes makes them unfeasible therapeutic targets for inhibiting MIC shedding. Here we identified an six-amino acid (6-aa) motif in the α3 domain of MIC that is critical for the interaction of MIC with ERp5 to enable shedding. Mutations in this motif prevented MIC shedding but did not interfere with NKG2D-mediated recognition of MIC. Our study suggests that the 6-aa motif is a feasible target to inhibit MIC shedding for cancer therapy.
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影响因子：
4.4
作者：
Wu, J;Groh, V;Spies, T
通讯作者：
Spies, T
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
影响因子：
3.1
作者：
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通讯作者：
Malemud, CJ
DOI：
10.1073/pnas.201238598
发表时间：
2001-09-25
影响因子：
11.1
作者：
Cerwenka, A;Baron, JL;Lanier, LL
通讯作者：
Lanier, LL
影响因子：
4.8
作者：
Raffaghello, L;Prigione, I;Pistoia, V
通讯作者：
Pistoia, V